Abstract
This cohort study assesses the outcome of oxaliplatin desensitization for patients with gastrointestinal cancers who experienced hypersensitivity reactions after oxaliplatin infusion.
Oxaliplatin, a third-generation platinum derivative, is a key drug for patients with gastrointestinal cancers in adjuvant or metastatic settings. Oxaliplatin-induced hypersensitivity reactions (HSRs) are reported in 12% to 24% of patients,1 with 0.5% experiencing anaphylaxis.2 Symptoms include rash, urticaria, angioedema, bronchospasm, and rarely hypotension,3 with potential life-threatening risk. The HSR incidence increases after multiple oxaliplatin infusions, suggesting an immediate type-I HSR.2 Skin prick tests can be performed and have a high negative predictive value.4 Premedication (antihistamines and corticosteroids) is not reliable to prevent recurrent HSR.2,3 Therefore, HSR often leads to oxaliplatin discontinuation, depriving patients of a potentially effective drug. Despite their complexity, desensitization protocols can be conducted in specialized centers, allowing oxaliplatin rechallenge. This cohort study examined the feasibility and safety of oxaliplatin desensitization in a French referral center.
Methods
Patients receiving an oxaliplatin-desensitization protocol from January 2013 to December 2020 were identified using the Gustave Roussy patient database. The Gustave Roussy Institutional Review Board approved this study. Participants provided oral consent. Data collection complied with review board guidelines. We followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.
Patients with gastrointestinal cancers, at least 1 HSR episode, and plans to pursue oxaliplatin with desensitization protocol after multidisciplinary specialized board meeting were included in the study. Patient characteristics and outcomes were retrospectively collected from hospital medical records (eTable in Supplement 1). The main outcome was HSR recurrence graded according to the Common Terminology Criteria for Adverse Events 4.0.
Oxaliplatin-desensitization protocol was conducted during an overnight hospital stay. Pretreatment included oral antihistaminergic (levocetirizine, 5 mg) 12 hours and 4 hours before oxaliplatin infusion, and intravenous infusion of corticosteroids (methylprednisolone, 120 mg) and antihistaminergic (dexchlorpheniramine, 5 mg) 1 hour before oxaliplatin infusion. Initial infusion rate of oxaliplatin was 1 mL/h, which was gradually increased every 30 minutes according to clinical tolerance (Table). Patients who were started on oxaliplatin-desensitization protocol were treated accordingly and stopped receiving fixed infusion rate perfusions. In case of HSR recurrence, oxaliplatin infusion was stopped; corticosteroids were readministered; and, if necessary, oxygen therapy was initiated with potential intensive care unit admission. H1 antihistamines were used as premedication; H2 antihistamines could also be administered in case of HSR recurrence.
Table. Oxaliplatin-Desensitization Protocol for Intravenous and Intra-arterial Hepatic Perfusion.
| Infusion time, h | Infusion rate, mL/h | Duration, min | Total dose, % |
|---|---|---|---|
| 0 | 1 | 30 | 0.09 |
| 0.5 | 3 | 30 | 0.28 |
| 1 | 8 | 30 | 0.75 |
| 1.5 | 20 | 30 | 1.85 |
| 2.5 | 50 | 30 | 4.6 |
| 3 | 100 | 30 | 9.26 |
| 3.5 | 150 | Until the end of the perfusion | 83.2 |
Results
Among the 54 patients (30 females [56%], 24 males [44%]; mean [SD] age, 55.2 [11.1] years) included, 44 (81%) had colorectal cancers. The first HSR episode was reported after a median (range) of 9 (1-31) oxaliplatin infusions; 33 patients (61%) had grade I to II events, and 21 patients (39%) had grade III to IV events (Figure). Three hundred five oxaliplatin-desensitization perfusions were administered, with a median (range) of 5 (1-20) perfusions per patient and a median delay of 7.9 months between the last oxaliplatin infusion and rechallenge. Median dose of oxaliplatin was 85 mg/m2 in a volume of 500 mL.
Figure. Study Flowchart.
HSR indicates hypersensitivity reaction; ICU, intensive care unit.
Forty-one patients (76%) experienced no HSR recurrence and completed the intended oxaliplatin perfusions, representing a 96% successful infusion rate. No association was found between HSR recurrence and oxaliplatin or corticosteroids dose related to patient weight.
Among the 21 patients with grade III to IV HSRs, oxaliplatin desensitization was efficient in 16 patients (79%). Among the 13 patients (24% of all patients, 4% of all infusions) who experienced recurrence, HSRs occurred after a median (range) of 2 (1-10) perfusions. No anaphylaxis, intensive care unit admission, or oxaliplatin-associated death occurred during desensitization protocol. Nevertheless, oxaliplatin was permanently discontinued for patients who experienced HSR recurrence.
Discussion
To our knowledge, this study involved the largest cohort of patients receiving an oxaliplatin-desensitization protocol with acceptable safety and feasibility after HSRs, especially grade III to IV HSRs. These results compare favorably with those of smaller studies5,6 (96% vs 81%-89% successful infusions). Although this study was limited by its retrospective design, it supports an oxaliplatin-desensitization strategy after oxaliplatin-induced HSRs.
eTable. Main Clinical Characteristics
Data Sharing Statement
References
- 1.Seki K, Senzaki K, Tsuduki Y, et al. Risk factors for oxaliplatin-induced hypersensitivity reactions in Japanese patients with advanced colorectal cancer. Int J Med Sci. 2011;8(3):210-215. doi: 10.7150/ijms.8.210 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Brandi G, Pantaleo MA, Galli C, et al. Hypersensitivity reactions related to oxaliplatin (OHP). Br J Cancer. 2003;89(3):477-481. doi: 10.1038/sj.bjc.6601155 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Lee C, Gianos M, Klaustermeyer WB. Diagnosis and management of hypersensitivity reactions related to common cancer chemotherapy agents. Ann Allergy Asthma Immunol. 2009;102(3):179-187. doi: 10.1016/S1081-1206(10)60078-6 [DOI] [PubMed] [Google Scholar]
- 4.Hong DI, Dioun AF. Indications, protocols, and outcomes of drug desensitizations for chemotherapy and monoclonal antibodies in adults and children. J Allergy Clin Immunol Pract. 2014;2(1):13-19. doi: 10.1016/j.jaip.2013.11.007 [DOI] [PubMed] [Google Scholar]
- 5.Cortijo-Cascajares S, Nacle-López I, García-Escobar I, et al. Effectiveness of oxaliplatin desensitization protocols. Clin Transl Oncol. 2013;15(3):219-225. doi: 10.1007/s12094-012-0909-9 [DOI] [PubMed] [Google Scholar]
- 6.Botsen D, Lepoix E, Mazza C, et al. Oxaliplatin-desensitization procedure is safe and feasible in an outpatient cancer unit in France. Support Care Cancer. 2019;27(9):3179-3182. doi: 10.1007/s00520-019-04863-5 [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
eTable. Main Clinical Characteristics
Data Sharing Statement